This invention relates to a novel peptide having potent antithrombin activity and, more particularly, to a synthetic peptide analogous to residues 54-75 of heparin cofactor II.
Heparin cofactor II (HCII) is an inhibitor of thrombin in plasma that is activated by dermatan sulfate or heparin. It is a 65,600 dalton glycoprotein member of the serpin (serine protease inhibitor) superfamily. The full sequence of 480 amino acids of the mature protein is disclosed by Blinder et al., Biochemistry 27, 752-759 (1988).
A short internal repeat amino acid sequence (Glu-Asp-Asp-Asp-Tyr-X-Asp, in which X=Ile or Leu) within HCII, beginning with Glu-56 and Glu-69, respectively, has been identified by Hortin et al., J. Biol. Chem. 261 (34), 15827-15830 (1986). These sequences flank two tyrosine residues at positions 60 and 73, respectively, which were shown to be sulfated in a human hepatoma-derived cell line (HepG2).
Further background information on HCII can be had by reference to the following illustrative papers: Tollefsen et al., J. Biol. Chem. 257, 2162-2169 (1982); Parker and Tollefsen, Ibid. 260, 3501-3505 (1985); and Hortin et al., Am. J. Clin. Pathol. 89, 515-517 (1988).